tbuckley/cabot-search huggingface dataset:
Deep neural networks and association with inpatient survival for patients admitted to the hospital with colon cancer undergoing open colectomy.
Authors: Aqsa Baig, Uzzam Ahmed Khawaja, Ayesha Liaquat Khan, Mohammad Hamza Khalil, Syed Musadiq Ali, Syed Abdul-Qader Qaudri, Tooba Tariq, Furqan Bin Irfan, Fahad Shabbir Ahmed
Journal: Journal of Clinical Oncology (2022)

e15537 Background: During hospitalization for colectomy patients with colon cancer may be at risk for mortality due to several reasons including underlying cancer, other comorbidities or age. Our aim was to develop a machine learning algorithm to predict end of admission mortality in patients undergoing colectomy for their cancer. We hypothesized that machine learning could be applied to patients undergoing open colectomy as part of their colon cancer treatment. Methods: All adult patients (&gt; 18 years) for the National in-patient Services (NIS) database 2014 was used to develop our algorithm. We extracted all patients with a diagnosis of cancer using the ICD-9 codes and all patients that underwent colectomy. We conducted a multivariate analysis to look at the risk factors that dictate mortality in these patients. We also developed a linear regression model and a deep learning algorithm to predict mortality in these patients. Results: We identified a total of 4120 patients that underwent open colectomy with colon cancer in the NIS 2014. We observed that several clinical and lab-based parameters were statistically significant for multivariate analyses while others were not. With most significant being all patients refined diagnosis related groups (APRDRG) risk mortality (HR = 6.20, 95%CI = 4.10-9.36), APRDRG severity (HR = 4.78, 95%CI = 3.27-7.00), chronic anemia (HR = 0.61, 95%CI = 0.40-0.94), coagulation disorders (HR = 2.32, 95%CI = 1.31-4.10), chronic electrolytes disorders (HR = 2.12, 95%CI = 1.39-3.24), neurological disorders (HR = 1.92, 95%CI = 1.11-3.32), underweight (low BMI) (HR = 2.40, 95%CI = 1.05-5.48), Hyperkalemia (HR = 2.40, 95%CI = 1.28-4.50), Acidosis (HR = 4.04, 95%CI = 2.64-6.19). In the machine learning analysis, we found out that our proposed DNN outperformed the RF with test set accuracy of 91.1%, sensitivity of 88.5%, specificity 91.2%, PPV of 24.7, NPV of 99.5% and AUROC of 0.968 [95%CI = 0.08-.014]. Conclusions: Our novel DNN model outperformed RF classifier models. The model is easy to implement, user friendly and with good accuracy. However, further external validation of the model is required.
Relationship between race and anemia in women undergoing surgery for gynecologic cancer.
Authors: Abigail Cain, Valerie Bianca Galvan-Turner
Journal: Journal of Clinical Oncology (2022)

e13529 Background: Anemia is associated with poor outcomes after gynecologic surgery and there is a paucity of data whether race modify its impact on outcome. The goal of this study is to estimate the anemia prevalence in women undergoing surgery for gynecologic cancer and to evaluate the relationship between preoperative anemia and postoperative morbidity and understand whether race and ethnicity modify this relationship. Methods: We performed a retrospective cohort study of patient’s undergoing surgery for a gynecologic malignancy between 2014 and 2019 using data from the National Surgical Quality Improvement Program. Multivariable logistic regression was used to determine adjusted odds for post operative morbidity with anemia. Interaction terms were entered into the model to test for effect modification by race and ethnicity. Results: We found that Black women were twice as likely to suffer from anemia then Caucasian women. In Caucasian women 79% had normal Hgb level, 16% mild anemia, 5% moderate anemia, and 0.5% with severe anemia. However, in Black women only 59% had normal Hgb level, with 30% having mild anemia, 10% moderate anemia, and 1% with severe anemia. We also found that the adjusted odds ratio of postoperative morbidity was higher in Black women with moderate and severe anemia than in Caucasian women. (Table). Logistic regression models to predict the probability of mortality for women with varying stages of anemia. Showing a difference in probability of morbidity between Black women and Caucasian women of undergoing gynecologic oncologic surgery. Conclusions: In this cohort of 56,240 patients who had surgery for a gynecologic malignancy we found that 24% had anemia. when treated may improve postoperative outcomes were more likely to have anemia than Caucasian women in this cohort. Black women had higher rates of postoperative morbidity at all levels of anemia, demonstrating continued disparities in care. Preoperative anemia is a modifiable risk factor that when treated may improve postoperative outcomes.[Table: see text]
Efficacy and safety of orelabrutinib in diffuse large B-cell lymphoma: A real-world analysis.
Authors: Peng-Peng Xu, Tingbo Liu, Zengjun Li, Zheng Li, Wei Huang, Keshu Zhou, Mingci Cai, Rong Shen, Weili Zhao
Journal: Journal of Clinical Oncology (2022)

e19556 Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. Recently, based on in-depth genomic analysis, new taxonomies for DLBCL have been proposed. Genetic subtype MCD is predominantly enriched with B-cell receptor-dependent NF-κB activation and well responded to Bruton’s tyrosine kinase (BTK) inhibitors. Ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) proved the efficacy in patients with MCD DLBCL in PHOENIX study. Orelabrutinib is a novel BTK inhibitor with excellent target selectivity. This study aimed to evaluate the efficacy and safety of orelabrutinib-containing regimens for the treatment of patients with MCD DLBCL in a real-world setting. Methods: Eligible patients with pathologically confirmed MCD DLBCL, regardless previous treatment, were included from 6 centers between January and December 2021. All patients received orelabrutinib-containing regimens and underwent at least one treatment response evaluation. Patients with known CNS lymphoma and primary mediastinal lymphoma were excluded. The primary endpoint was complete response rate (CRR) assessed by investigator using PET-CT per the 2014 Lugano Response Criteria for Non-Hodgkin Lymphoma. Safety was assessed by adverse events (AEs) referring to Common Terminology Criteria for AEs version 5.0. Results: Fourteen patients (10 males) were included. The median age was 66 (range 45-77) years, and 35.71% (5/14) documented ≥2 extranodal involved sites. Most patients had an Eastern Cooperative Oncology Group score of 0-1 (9/14, 64.29%), Ann Arbor Stage III-IV disease (11/14, 78.57%), elevated lactate dehydrogenase (9/14, 64.29%), and International Prognostic Index score ≥3 (8/14, 57.14%). All patients received orelabrutinib 150 mg once daily. Among them, 8 (57.14%) were treated with R-CHOP or rituximab plus etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (R-EPOCH) as first-line therapy, and 6 (42.86%) with rituximab plus ifosfamide, carboplatin and etoposide (R-ICE), R-CHOP or rituximab with lenalidomide as second-line therapy. The CRR for the first-line and second-line therapy were 75.00% and 66.67%, respectively. The most common AEs were hematologic (platelet count decrease, white blood count decrease or lymphocyte count decrease), and non-hematologic AE was infection (urinary or respiratory). Reported AEs were generally manageable and resolved soon after supportive treatment. AEs associated with off-target activities such as atrial fibrillation, diarrhea, and major hemorrhage were not reported. Conclusions: Orelabrutinib-containing regimens demonstrated encouraging efficacy and well-tolerated safety profile among patients with MCD DLBCL. A large-scale prospective clinical study is on registration, which would offer a new potential therapeutic option for patients with MCD DLBCL.
D3S-001, a highly potent, selective, and differentiated covalent inhibitor of KRAS G12C: Human dose prediction and first‐in‐human (FIH) trial design.
Authors: Jingtao Lu, Jing Zhang, Zhiqiang Zheng, Cheng Chen, Jia Wang, Janet Chen, Jiang Lu, Haopeng Rui, Allison Wang, Zhi Jian Chen
Journal: Journal of Clinical Oncology (2022)

e15087 Background: Effective inhibition of G12C mutated KRAS is believed to be critical for anti-tumor efficacy in KRAS-driven cancers. D3S-001 is a potent and highly differentiated KRAS G12C inhibitor, which demonstrates rapid and near complete target inhibition and strong anti-tumor activity in preclinical cell line and animal models [Preclinical characterization of D3S-001, a highly potent, selective, and differentiated covalent inhibitor of KRAS G12C, ASCO 2022 Abstract #378099]. The current study utilizes pharmacokinetic (PK) modeling to predict the extent of KRAS G12C target inhibition at the proposed clinical dose range. Methods: Allometric scaling and non-linear fixed effect modeling were used to predict human PK profiles from DMPK data in animals. Human in vivo target inhibition was calculated based on human PK predictions, free drug fraction and results from in vitro target engagement assay. A First-in-Human (FIH) study was designed to investigate D3S-001 monotherapy in subjects with advanced solid tumors having a KRAS G12C mutation. Six dose escalation cohorts will be investigated, starting from 50mg QD. Results: Based on a GLP toxicology study in dogs, the highest non-severely toxic dose (HNSTD) was determined to be 20 mg/kg/day. Per ICH S9, a 20 mg/kg/day dose in dog supports a FIH starting dose of 110 mg. To ensure an additional safety margin, a lower starting dose of 50 mg was proposed. At 50 mg QD, the predicted human exposure (C max 60 nM, C average 49 nM, C trough 31 nM) is expected to achieve ̃70% target inhibition at 2 hours after dosing. In NCI-H358 mouse xenograft model, this exposure is associated with 94% tumor growth inhibition (TGI). Safety margins based on C max and AUC comparing to dog HNSTD are 17-fold and 9-fold, respectively. At 100 mg QD, the predicted human exposure (C max 120 nM, C average 98 nM, C trough 63 nM) is expected to achieve ̃95% target inhibition. This exposure is associated with tumor regression of 72% in the NCI-H358 mouse xenograft model. At dose levels higher than 100 mg QD, predicted human exposures are expected to consistently achieve &gt;95% target inhibition starting 1 hour after dosing. These exposures are associated with deeper levels of tumor regression of 97%. Moreover, even at 400 mg QD, predicted human plasma concentrations are still below dog plasma concentration of 443 nM, C average at HNSTD. Conclusions: D3S-001 is predicted to achieve rapid and consistently efficacious KRAS G12C target inhibition in humans at proposed clinical dose range. This high degree of KRAS G12C inhibition over the dosing interval may translate into greater clinical benefit to patients with KRAS G12C mutations comparing with other clinical-stage KRAS G12C inhibitors. Clinical data from the FIH study will be evaluated and compared to preclinical predictions.
Gender distribution of speakers and moderators at the Russian cancer congresses in 2016-2021.
Authors: Sheyda Abdullaeva, Valentina Shamrikova, Vadim Gushchin, Polina Shilo
Journal: Journal of Clinical Oncology (2022)

e18516 Background: Gender equity in world medicine has recently received widespread attention. There is evidence that men and women may practice medicine differently, and better women representation in the oncology workforce and leadership may improve patient outcomes. Nevertheless, women continue to be under-represented in the big academic events, also in oncology. Methods: A retrospective analysis of the programs of major annual Russian oncological congresses: Russian Oncology Congress and White Nights was carried out. The gender of speakers and moderators was collected from 2016 to 2021. Participation of the same person in several sessions or in different roles in one session was considered as a separate case. Data are presented by descriptive statistics, and differences between groups were assessed using the Сhi-square test. P-values below 0.05 were considered statistically significant. Results: The data of 1350 sessions, 796 moderators and 1756 speakers were available for analysis. For the analyzed period of time (2016-2021), the total percentage of female speakers was 42.2% (n = 3120), the percentage of female moderators was 34.8% (n = 1196). There were more male speakers than female speakers in surgical sessions (87.9% and 12.1% p &lt; 0.001). There were more male moderators than women in surgical sessions (92.4% and 7.6% p &lt; 0.001). There were more male speakers than female speakers in chemotherapy sessions (55.2% and 44.8% p &lt; 0.001). There were more male moderators than women in chemotherapy sessions (58.9% and 41.1% p &lt; 0.001). Conclusions: The gender inequality in oncology is more pronounced in the leadership positions in male-dominated specialties such as surgical oncology. Better women representation in the oncology leadership may be an effective strategy to improve oncology care in Russia
Novel use of clinical pathways to identify poor prognosis lung cancer patients: Implementation and outcomes.
Authors: David Michael Jackman, Matthew Rice, Nicholas Virkler, Belinda Desravines, Victoria H. Selesnick, Michael Scalzo, Jocelyn H. Siegel, James A. Tulsky, Joseph O. Jacobson
Journal: Journal of Clinical Oncology (2022)

1589 Background: Cancer patients in the last year of life have different clinical needs and evolving goals of care. Using our oncology decision-support pathways to help clinicians consistently identify such patients in a systematic and prospective fashion, at a discrete moment in the care trajectory, may be an important step towards matching the care of these patients with their stated goals. Methods: Medical oncologists from each disease group at the Dana-Farber Cancer Institute (DFCI) were tasked with identifying clinical settings in each oncology care pathway associated with an expected median survival of &lt; 12 months. This information was embedded into the underlying data model of the pathways platform, allowing us to determine how often clinicians navigated through each poor prognosis node. Results: From 3/1/20 – 6/30/21, there were 264 navigations in 205 unique lung cancer patients receiving standard of care (i.e., not on clinical trial) for a clinical condition associated with poor prognosis. Overall, the median overall survival from the time of a patient’s first navigation through a poor prognosis node during the defined study period was 6.4 months. Table lists outcomes for each specific setting. Patients with squamous or small cell lung cancer being treated in or beyond the third-line setting had notably poor outcomes, with less than a third of these patients surviving 6 months from the time of navigation. Conclusions: A clinical pathways platform can be a key tool in designating clinical scenarios associated with poor prognosis and identifying patients who may be particularly at risk. Pathways analytics provide real-world evidence corroborating the expected poor prognosis based on published studies and can identify specific clinical subsets for whom specific resources are warranted. By embedding this into the pathways data model, we aim to alert physicians to conduct goals of care conversations, offer supportive care resources, and match patients to appropriate treatment options and clinical trials. [Table: see text]
Smoking cessation counseling in patients with active malignancy.
Authors: Zachary M Avigan, Leora S Boussi, Kenneth J. Mukamal
Journal: Journal of Clinical Oncology (2022)

e18655 Background: Tobacco smoking increases risk of multiple malignancies, most notably lung cancer, and is a leading cause of premature morbidity and mortality. Tobacco cessation counseling is effective in assisting patients to quit smoking and improving health outcomes, but over one third of smokers report receiving no counseling by healthcare providers. In this study, we investigated rates of tobacco cessation education at ambulatory visits among patients with active malignancy. Methods: We identified ambulatory visits among current smokers with a diagnosis of malignancy using the National Ambulatory Medical Care Survey (NAMCS), a nationally representative sample of ambulatory visits in the US, from 2008 to 2018. We first determined weighted rates of documented smoking cessation counseling. We next evaluated sociodemographic characteristics, provider and visit type, and chronic conditions as determinants of counseling in this population using logistic regression. Results: We identified 2,437 total visits during the study period, representing an estimated 48.9 million such visits in the US. In this cohort, smoking cessation counseling was provided at 14.2% (95% confidence interval [CI] 12.1-16.7%) of visits. Patients were significantly less likely to receive counseling with older age (adjusted OR 0.97 per year of age; 95% CI 0.96-0.98) and less likely in surgical (OR 0.49; 95% CI 0.32-0.75) or medical subspecialties (OR 0.60; 95% CI 0.36-0.99) compared to primary care visits. Sex, race, year of visit, insurance type, and previous visit to the same provider were not significantly related to receipt of counseling. Patients with concomitant COPD were substantially more likely to receive counseling (OR 3.50; 95% CI 2.21-5.53), with 28.4% (95% CI 21.5-36.4%) of such visits including tobacco cessation education. Conclusions: Tobacco smoking is a modifiable risk factor associated with multiple malignancies and substantial non-neoplastic morbidity and mortality. Nonetheless, smokers with current malignancy receive smoking cessation counseling at only about one in seven outpatient visits, with lower frequency with advanced age and at subspecialty visits. As more effective treatments improve survival for cancer patients, further work is needed to improve tobacco cessation efforts that could improve survival and quality of life.[Table: see text]
Longitudinal molecular analysis of tumor exome and transcriptome to evaluate clonal evolution and identify novel therapeutic targets in thymoma.
Authors: Christopher Sheild Nabel, Anna Kurilovich, Aleksandra Lopareva, Dora Dias-Santagata, Nikita Batashkov, Nara Shin, Abner Louissant
Journal: Journal of Clinical Oncology (2022)

e20624 Background: The rarity of thymic epithelial tumors has limited mechanistic understanding of tumor biology and the rational identification of potential therapeutic targets for patients with advanced disease. While the Cancer Genome Atlas Project enabled multi-omic profiling of thymic epithelial tumors, the majority of samples were early-stage and chemotherapy-naïve. Furthermore, next generation sequencing for patients with advanced disease often provides only a limited breadth of genome coverage. The genetic changes in thymic epithelial tumors that evolve through disease progression and treatment represent a current knowledge gap and opportunity for reassessment of new therapeutic targets. Methods: To address these points, we conducted whole exome and bulk RNA transcriptome sequencing for serially-collected FFPE archival tumor samples from a patient with Stage IVA, WHO B2/B3 thymoma using the BostonGene Tumor Portrait Test version 1.3. Samples analyzed include the initial primary tumor resected without induction treatment; two subsequent, metachronous pleural recurrences resected without any induction treatment; and a third pleural metastasis resected following two cycles of induction chemotherapy with Cisplatin/Adriamycin/Cyclophosphamide without interval radiographic evidence of treatment response. Results: Tumor characteristics were largely consistent with prior molecular studies, and without significant evidence of major clonal evolutionary changes based on single nucleotide polymorphisms, insertions/deletions or copy number alterations. Tumor mutational burden was recurrently low (&lt; 1 mutation per megabase) with stable microsatellite status. EGFR copy number gain was observed (+1 copy) across recurrent pleural resection specimens. While the degree of copy number gain did not change with disease progression, increasing EGFR transcript counts were observed and evaluated by IHC. Other notable therapeutic biomarkers included absent TGFB1 and present VEGFA expression. Collective RNA-based gene expression changes were compared with the Thymic TCGA cohort for reference. Conclusions: Our analysis illustrates the narrow clonal evolution of a thymic epithelial tumor through treatment—both with and without the selective pressures of induction chemotherapy. This suggests that the genomic features of advanced thymoma may reflect the treatment-naïve state as described in the TCGA, one marked by a low mutational burden but with recurrent copy number alterations in select genes. Complementary transcriptome sequencing identified EGFR expression as a promising therapeutic target for further study. Taken together, these findings illustrate the hypothesis-generating potential for deep molecular analysis with whole exome and transcriptome sequencing to improve the understanding of rare tumors.
The landscape of RAS mutations and hotspots in Chinese patients with solid tumors.
Authors: Mei Li, Han Li
Journal: Journal of Clinical Oncology (2022)

e15114 Background: As one of the most commonly oncogene, RAS mutations ( HRAS, NRAS, KRAS) have been confirmed closely related to the tumorgenesis and proliferation of solid tumors.Yet a comprehensive analysis of RAS mutations and hotspots in Pan-Cancers of Chinese is lacking. Herein, we firstly report the RAS mutation frequency and hotspots features based on a Chinese pan-cancers database, aiming to evaluate the correlation between RAS mutation status and the clinical implication of human cancers. Methods: This was a retrospective study in patients with solid tumors performed NGS panel based on tissue or blood samples in ChosenMed. A cohort of 5420 samples consisting of 22 solid tumor types from Chinese was analyzed to exhibit the landscape of RAS mutations and hotspots. Results: According to our database, the total mutation frequency of KRAS, NRAS, and HRAS was 17.34% (940/5429) in 22 tumor types, of which pancreatic cancer, bowel cancer and endometrial eancer occurred more commonly (with mutation frequencies of 64.04%, 46.07%, and 26.32%, respectively). The RAS mutation hotspots mainly consisted of G12, G13, and Q61, which exhibited preference in each RAS isoforms. For KRAS, G12 mutation site occupied 76.99% (619/804) of all mutations, and mutations at Q61 accounted for 52.83% (28/53) of NRAS mutations. Lastly, HRAS mutations at above three sites presented lowest proportion of 16.83% (17/101). Conclusions: This study firstly reports the RAS mutation characters in pan-cancers based on the Chinese database, which has provided RAS hotspots details for helping to screen more tumor patients who are sensitive to RAS inhibitors. Also, further investigation should be performed for the development of RAS-targeting drugs.